Pranoprofen is an acidic non-steroidal anti-inflammatory drug which is a propionic acid derivative, is useful for inflammatory diseases in the ophthalmic field such as keratoconjunctivitis in an extraocular area and an anterior segment of the eye, and has been put into practice in the form of an ophthalmic soluton. Pranoprofen can stimulate the eyes and, therefore, a variety of attempts have been made to suppress the irritation in order to prepare ophthalmic solutions. For example, there have been proposed a method by addition of boric acid (Japanese Laid-open Patent Publication No. 60-184013), a method by addition of carbonate (Japanese Laid-open Patent Publication No. 5-186349) and a method by addition of acetate ion (Japanese Laid-open Patent Publication No. 7-17863)to reduce such irritation.
On the other hand, an attempt at preparing ophthalmic solutions and intraocular Irrigating solutions containing an organic amine have been also made. For example, in a case of an ophthalmic solution containing sulfa drugs, there has been disclosed a method for making it possible to solubilize sulfa drugs and enhancing the preserative properties by addition of an alkanolamine such as monoethanolamine, diethanolamine or triethanolamine in ophthalmic solutions containing a sulfa drug and, thereby, (Japanese Patent Publication No. 1-29170, Japanese Laid-open Patent Publication No. 59-89616 and Japanese Laid-open Patent Publication No. 61-12617). In addition, there have been also disclosed diclofenac sodium ophthalmic solutions containing tromethamine or a homologue thereof having 10 or less carbon atoms as preseratives and a stabilizing agent (Japanese Laid-open Patent Publication No. 62-242617, Japanese Laid-open Patent Publication No. 62-242618), and intraocular irrigating solutions containing chondroitin sulfate in which 4-(2-hydroxyethyl)-1-(2-sulfoethyl)piperazine (hereinafter referred to as "HEPES") is formulated (PCT WO87/00753 and U.S. Pat. No. 4725586).
However, there has not been reported yet preparations of ophthalmic solutions containing pranoprofen as an active ingredient and in which an organic amine is formulated.
It is an interesting theme to find ophthalmic solutions containing pranoprofen as an active ingredient, which has an excellent stability and little irritation to eyes.
An object of the present invention is to provide ophthalmic solutions containing pranoprofen as an active ingredient, which has no change in the composition, an excellent stability and little irritation to eyes.
In order to find pranoprofen ophthalmic solutions having an excellent stability and little irritation to eyes, the present inventors studied extensively. As a result, the present inventors found that ophthalmic solutions which have no change in the composition, an excellent stability and little Irritation to eyes can be prepared by addition of an organic amine such as tromethamine or HEPES.